The objectives of this study are to develop an understanding of the basic biology of the arterial endothelium, and of the mechanisms governing endothelial permeability to macromolecules. Using scanning and transmission electron microscopy in conjunction with histochemical and biochemical techniques, the structure of the arterial endothelium and intima will be examined under normal conditions, and under altered conditions induced by three model systems. The endothelium and intima will be examined both prior to, and during, early lesion development in dietary-induced hypercholesterolemia, and secondly, at various times following experimental aortic coarctation. The Evans Blue Model of spontaneously occurring increased aortic permeability to macromolecules will be examined in detail in conjuntion with the above two model systems in pigs. In addition, the structure of arterial endothelium and intima will be examined following acute infusions of vasoactive compounds. The permeability characteristics of arterial endothelium in each of these systems will be examined using ferritin, myoglobin and horseradish peroxidase as intravenous particulate tracers at the ultrastructural level, and uptake of these tracers will be quantitated in the first two instances. These studies hope to gain an insight into the structure and permeability characteristics of arterial endothelium under a variety of conditions, and to relate these parameters to the process of atherogenesis.